Ultrastructural examination of biopsies showing Helicobacter pylon associated chronic gastritis reveals close attachment between gastric surface epithelial celis and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response ofintestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with Hpyloni positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune responsenamely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors.
Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy. Cancer Res; 73(23); 6886-99. Ó2013 AACR.
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